Gene Expression Classifier Reveals Prognostic Osteosarcoma Microenvironment Molecular Subtypes.
Gene Expression Classifier Reveals Prognostic Osteosarcoma Microenvironment Molecular Subtypes.
复制标题
基因表达分类器揭示预后骨肉瘤微环境分子亚型
DOI：
10.3389/fimmu.2021.623762
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发表时间：
2021
影响因子：
7.3
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Song YJ;Xu Y;Deng C;Zhu X;Fu J;Chen H;Lu J;Xu H;Song G;Tang Q;Wang J
骨肉瘤（OSA）是最常见的骨恶性肿瘤，并表现出高度的分子表型异质性。本研究旨在通过开发基于肿瘤微环境基因表达谱的分类系统来表征 OSA 的分子特征。使用 TARGET 计划中 OSA 患者的标本和临床信息进行综合分析。使用矩阵分解方法，我们确定了两种与预后显着相关的分子亚型：S1（浸润型）和S2（逃逸型）。两种亚型均表现出独特的功能意义特征和细胞浸润特征。我们确定，与 S2 亚型相比，S1 亚型的免疫和基质浸润更为丰富。此外，免疫检查点 PDCD1LG2 和 HAVCR2 的较高表达与预后改善相关，而更好的化疗反应与 S1 亚型中 FAP 阳性成纤维细胞相关。或者，S2亚型的特征是缺乏有效的细胞毒性反应和主要组织相容性复合物I类分子表达的丧失。最终生成基因分类器以实现 OSA 分类，并使用 GSE21257 验证集确认结果。基于 47 个 OSA 原发性肿瘤，评估和验证了成纤维细胞和/或纤维化与 CD8+ 细胞的百分比及其对化疗的临床反应之间的相关性。这项研究建立了一个新的 OSA 分类系统，用于对 OSA 患者风险进行分层，从而进一步定义 OSA 的遗传多样性，并提高个性化治疗的效率。
Osteosarcoma (OSA) is the most common bone malignancy and displays high heterogeneity of molecular phenotypes. This study aimed to characterize the molecular features of OSA by developing a classification system based on the gene expression profile of the tumor microenvironment. Integrative analysis was performed using specimens and clinical information for OSA patients from the TARGET program. Using a matrix factorization method, we identified two molecular subtypes significantly associated with prognosis, S1 (infiltration type) and S2 (escape type). Both subtypes displayed unique features of functional significance features and cellular infiltration characteristics. We determined that immune and stromal infiltrates were abundant in subtype S1 compare to that in subtype S2. Furthermore, higher expression of immune checkpoint PDCD1LG2 and HAVCR2 was associated with improved prognosis, while a preferable chemotherapeutic response was associated with FAP-positive fibroblasts in subtype S1. Alternatively, subtype S2 is characterized by a lack of effective cytotoxic responses and loss of major histocompatibility complex class I molecule expression. A gene classifier was ultimately generated to enable OSA classification and the results were confirmed using the GSE21257 validation set. Correlations between the percentage of fibroblasts and/or fibrosis and CD8+ cells, and their clinical responses to chemotherapy were assessed and verified based on 47 OSA primary tumors. This study established a new OSA classification system for stratifying OSA patient risk, thereby further defining the genetic diversity of OSA and allowing for improved efficiency of personalized therapy.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
结构细胞是器官特异性免疫反应的关键调节剂。
影响因子：
64.8
作者：
Krausgruber T;Fortelny N;Fife-Gernedl V;Senekowitsch M;Schuster LC;Lercher A;Nemc A;Schmidl C;Rendeiro AF;Bergthaler A;Bock C
通讯作者：
Bock C
DOI：
10.1038/s41577-019-0218-4
发表时间：
2020-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Kalbasi A;Ribas A
通讯作者：
Ribas A
影响因子：
15.9
作者：
Lu, Jinchang;Song, Guohui;Wang, Jin
通讯作者：
Wang, Jin
DOI：
10.1073/pnas.1320318110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Feig, Christine;Jones, James O.;Fearon, Douglas T.
通讯作者：
Fearon, Douglas T.